Investigating the Multimodal Mechanism of a Polyherbal Anti-Diabetic Preparation Using 3T3-L1 adipocytes, C2C12 myotubes, and βTC-6 β-Cell Line Models

Introduction

Hyperglycaemia is a complicated condition that includes reduced production of insulin, resistance towards insulin, and oxidative imbalance. Current therapies often have limited efficacy and adverse effects, prompting interest in safer, multitarget alternatives. Traditional polyherbal formulations have been used for diabetes, yet their mechanisms remain underexplored.

Objectives

This study evaluated the antidiabetic potential of a standardized Polyherbal Preparation (EPHP 1) containing dried Tinospora cordifolia leaves, dried Cinnamomum zeylanicum bark, and dried Trigonella foenum-graecum and Nigella sativa seeds.

Materials and Methods

Phytochemical standardization of ethanolic extracts performed. In vitro experiments included inhibition of α-glucosidase and α-amylase, glucose absorption in 3T3-L1 adipocytes and C2C12 myoblasts, and insulin secretion by stimulation of glucose in βTC-6 cells. The MTT test was used to evaluate cytotoxicity. Anti diabetic ability was determined in diabetic rats induced by streptozotocin. In vivo hepatic antioxidant parameters (SOD, CAT, GSH, MDA) was also evaluated.

Results

EPHP 1 strongly inhibited α-glucosidase and α-amylase. In cells, it enhanced glucose uptake (up to 149% in 3T3-L1, 142% in C2C12) and increased insulin secretion (176% of control). In vivo, EPHP 1 (400 mg/kg) reduced blood glucose to 126.4 mg/dL by day 28 and restored antioxidant defenses, with no cytotoxicity observed.

Conclusion

These findings indicate that EPHP 1 exerts potent antihyperglycemic effects via digestive enzyme inhibition, improved peripheral glucose uptake, enhanced insulin secretion, and attenuation of oxidative stress, providing scientific validation for its traditional use and supporting its potential as a safe, multitarget adjunct therapy for T2DM.